Premium
Distribution of oxytetracycline to tissue cages and granuloma pouches in calves and effect of acute inflammation on distribution to tissue cages
Author(s) -
BENGTSSON B.,
LUTHMAN J.,
JACOBSSON S. O.,
EKMAN S.
Publication year - 1991
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.1991.tb00852.x
Subject(s) - oxytetracycline , pharmacokinetics , lipopolysaccharide , chemistry , inflammation , distribution (mathematics) , medicine , antibiotics , biochemistry , mathematics , mathematical analysis
The effect of acute inflammation on oxytetracycline (OTC) distribution was studied in a tissue cage model in calves. An acute inflammatory reaction was induced in tissue cages by injecting lipopolysaccharide (LPS) from Salmonella typhimurium . The distribution of OTC to tissue cage fluid (TCF) was also compared with distribution to fluid from granuloma pouches (GPF). Tissue from LPS‐injected cages showed histological changes indicating an acute inflammatory reaction. Concentrations of OTC were higher in LPS cages than in controls; at 1, 2, 4 and 10h the difference was statistically significant (P<0.05). Numerically the overall elimination rate constant (k el ) was larger, elimination half‐life (t 1/2 ) shorter, peak concentration (C max ) higher, and time of peak concentration (T max ) shorter in LPS cages than in controls. The area under the curve (AUC) of OTC was greater and the ratio AUC TCF / AUC serum was higher in LPS cages than in controls. Although statistically significant differences were not found for all the pharmacokinetic parameters, it was concluded that distribution to and elimination from LPS cages were both faster than in controls. Concentration‐time profiles of OTC were similar in TCF and GPF in that concentrations were lower and elimination was more prolonged than in serum. Levels were higher in GPF than in TCF up to 3h after injection; thereafter the relationship was reversed. Distribution to and elimination processes from GPF appeared to be faster than from TCF as numerically k el was higher, t 1/2 shorter and T max shorter in GPF than in TCF. It was concluded that the granuloma pouch model and the tissue cage model have similarities in distribution and elimination patterns and that differences are most probably due to differences in the ratio of the surface area to the volume.